title: VSL#3 probiotic modifies mucosal microbial composition but does not reduce colitis-associated colorectal cancer.
abstract: Although probiotics have shown success in preventing the development of experimental colitis-associated colorectal cancer (CRC), beneficial effects of interventional treatment are relatively unknown. Here we show that interventional treatment with VSL#3 probiotic alters the luminal and mucosally-adherent microbiota, but does not protect against inflammation or tumorigenesis in the azoxymethane (AOM)/Il10⁻/⁻ mouse model of colitis-associated CRC. VSL#3 (10⁹ CFU/animal/day) significantly enhanced tumor penetrance, multiplicity, histologic dysplasia scores, and adenocarcinoma invasion relative to VSL#3-untreated mice. Illumina 16S sequencing demonstrated that VSL#3 significantly decreased (16-fold) the abundance of a bacterial taxon assigned to genus Clostridium in the mucosally-adherent microbiota. Mediation analysis by linear models suggested that this taxon was a contributing factor to increased tumorigenesis in VSL#3-fed mice. We conclude that VSL#3 interventional therapy can alter microbial community composition and enhance tumorigenesis in the AOM/Il10⁻/⁻ model.
authors.affiliation: Department of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Janelle C
authors.initials: JC
authors.lastname: Arthur
authors.forename: Raad Z
authors.initials: RZ
authors.lastname: Gharaibeh
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Uronis
authors.forename: Ernesto
authors.initials: E
authors.lastname: Perez-Chanona
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
authors.forename: Sarah
authors.initials: S
authors.lastname: Tomkovich
authors.forename: Marcus
authors.initials: M
authors.lastname: Mühlbauer
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fodor
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003092:Colitis / Q000150:complications* / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D019936:Probiotics / Q000008:administration & dosage / Q000378:metabolism*